Uterine Cancer

Question 1

Causes of DUB?

Answer 1

Endometrial polyps - COMMON and often occur around/after the menopause

Endometrial hyperplasia:

• Simple
• Complex
• Atypical (precursor of carcinoma) - this refers to the cytology (appearance of cells)

Question 2

Causes of endometrial hyperplasia?

Answer 2

Often unknown

May be due to persistent oestrogen stimulation

Question 3

PC of endometrial hyperplasia?

Answer 3

Abnormal bleeding:

• DUB
• Post-menopausal bleeding

Question 4

Describe simple endometrial hyperplasia

Answer 4

Simple - distribution is generalised, affecting the glands and stroma; the glands are dilated, but not crowded

Cytology is normal

Question 5

Describe complex endometrial hyperplasia

Answer 5

Complex - focal distribution, affecting the glands, which are crowded

Cytology is normal

Question 6

Describe atypical endometrial hyperplasia

Answer 6

Atypical - focal distribution, affecting the glands, which are crowded

Cytology is atypical

NOTE - with this, there is a high risk of developing OR of having concurrent endometrial carcinoma; for this reason, it is treated with a hysterectomy

Question 7

Occurrence of endometrial carcinoma?

Answer 7

Peak incidence 50-60 years

It is uncommon <40 years; young women, consider an underlying predisposition, e.g: PCOS or Lynch syndrome

Question 8

2 main groups of endometrial carcinoma?

Answer 8

Endometrioid carcinoma (more common) - the precursor lesion is atypical hyperplasia

Endometrial carcinoma is related to unopposed oestrogen and is graded I-III

Serous carcinoma (less common) - the precursor lesion is serous intra-epithelial carcinoma; this cancer is not assoc. with unopposed oestrogen

Serous carcinoma is more common in elderly, post-menopausal women; it is always aggressive and so it is not graded

Question 9

PC of endometrial carcinoma?

Answer 9

Generally presents with abnormal bleeding

Question 10

Macroscopic appearance of endometrial carcinoma?

Answer 10

Large, polypoid uterus

Question 11

Microscopic appearance of endometrial carcinoma?

Answer 11

Majority are adenocarcinomas and most are well-differentiated

Question 12

Spread of endometrial carcinoma?

Answer 12

Directly into the myometrium and cervix (this typically occurs)

Lymphatic spread

Haematogenous spread

Question 13

Mutation that is often present in serous endometrial carcinomas?

Answer 13

TP53 mutations (this is checked and should be +ve, to help confirm the diagnosis)

Question 14

What are the type I endometrial carcinoma tumours?

Answer 14

Endometrioid and mucinous phenotypes - assoc. with atypical hyperplasia as the precursor lesion

There are underlying PTEN, KRAS and PIK3CA mutations

These often have microsatellite instability, i.e: mutations occur in short projections of DNA

NOTE - endometrioid carcinoma has a good prognoses, as it is usually confined to the uterus at presentation

Question 15

Risk factors for endometrial carcinoma?

Answer 15

Obesity

Lynch syndrome

Question 16

Why is obesity assoc. with endometrial carcinoma?

Answer 16

Increased risk is due to endocrine and inflammatory effects of adipose tissue

The adipocytes express aromatase, which converts ovarian androgens into oestrogens that induce endometrial proliferation

Sex-hormone binding globulin levels are lower in obese women, so the level of unbound, biologically active hormone is higherInsulin action is often altered in obese women:

• Level of insulin-binding globulins reduced
• Free insulin levels elevated - insulin / insulin-like growth factors (IGF) exert a proliferative effect on the endometrium

Question 17

How to reduce the risk of endometrial carcinoma assoc. with obesity?

Answer 17

Weight loss

Question 18

What is Lynch syndrome?

Answer 18

AKA Hereditary Non-Polyposis Colorectal Cancer (HNPCC)

A cancer predisposition syndrome that occurs due to inheritance of a defective DNA mismatch repair gene; it has autosomal dominant inheritance (50% chance if 1 parent has it)

In addition to colorectal cancer, there is a high risk of:

• Endometrial cancer
• Ovarian cancer

Question 19

Identifying tumours that occur due to Lynch syndrome?

Answer 19

Immunohistochemistry staining (for mismatch repair proteins)

Test cancer tissue for MSI (microsatellite instability), a characteristic of defective mismatch repair

Question 20

What are type II endometrial carcinoma tumours?

Answer 20

Serous and clear cell types; the precursor lesion is serous endometrial intraepithelial carcinoma

Assoc. with underlying TP53 mutation and over-expression

Question 21

Spread of type II endometrial carcinoma tumours?

Answer 21

Spreads along fallopian tube mucosa and peritoneal surfaces, so it can present with extra-uterine disease

Question 22

Treatment of endometrial carcinoma?

Answer 22

Surgery is usually more extensive

Adjuvant chemo/radiotherapy is used more frequently

NOTE - this is because they are more aggressive than endometrioid/mucinous carcinoma

Question 23

Histological characteristics of serous carcinoma?

Answer 23

Complex papillary and/or glandular architecture with diffuse, marked nuclear pleomorphism

Question 24

Staging of endometrial carcinoma?

Answer 24

Stage I - confined to uterus:

• Stage IA - no OR <50% myometrial invasion
• Stage IB - invasion ≥50% of myometrium

Stage II - tumour invades the cervical stroma

Stage III - local and/or regional tumour spread:

• Stage IIIA - tumour invades serosa of uterus and/or adnexae
• Stage IIIB - vaginal and/or parametrial involvement
• Stage IIIC - metastases to pelvic and/or para-aortic lymph nodes

Stage IV - tumour invades bladder and/or bowel mucosa (IVA) and/or distant metastases (IVB)

Question 25

Prognosis of endometrial carcinoma?

Answer 25

Depends on the following: * Stage * Histological grade * Depth of myometrial invasion

Question 26

Treatment of endometrial carcinoma?

Answer 26

Hysterectomy Chemo/radiotherapy

Question 27

Explain the histological grading of endometrial carcinoma

Answer 27

Grade 1 - 5% or less solid growth Grade 2 - 6-50% solid growth Grade 3 - \>50% solid growth NOTE - serous and clear cell carcinoma are not formally graded

Question 28

Other endometrial tumours?

Answer 28

Endometrial stromal sarcoma - arises from endometrial stroma; it is rare Carcinosarcoma - mixed tumour, with malignant epithelial and stromal elements

Question 29

Grades of endometrial stromal sacroma?

Answer 29

Low-grade endometrial stromal sarcoma High-grade endometrial stromal sarcoma (increased atypia and proliferative activity); more likely to cause death

Question 30

Spread of endometrial stromal sarcoma?

Answer 30

Infiltrate myometrium and often lymphovascular spaces

Question 31

Presentation of endometrial stromal sarcoma?

Answer 31

Abnormal uterine bleeding Initial presentation may be with metastasis (most commonly at the ovaries oor lung) NOTE - even with treatment, recurrence with, e.g: lung nodules, is common, due to lymphovascular lesions; even the low-grade tumours are capable of doing this

Question 32

Staging of endometrial stromal sarcoma?

Answer 32

Different staging system from endometrial cancer

Question 33

Occurrence of carcinomasacromas?

Answer 33

\<5% of uterine malignancies

Question 34

Constituents of carcinosarcoma?

Answer 34

High grade carcinomatous and sarcomatous elementsHeterologous elements commonly seen in ~50% cases (rhabdomyosarcoma, chrondrosarcoma, osteosarcoma) NOTE - presence of rhabdomyosarcomatous component has the worst prognosis

Question 35

Prognosis of carcinosarcoma?

Answer 35

Usually assoc. with poor outcome

Question 36

Staging of carcinosarcoma?

Answer 36

Same staging system as endometrial cancers

Question 37

Tumours of the myometrium?

Answer 37

Leimyoma (AKA fibroid) - very common; histology is similar to that of smooth muscle Leiomyosarcoma - rare but the most common uterine sarcoma; display a spindle cell morphology

Question 38

Presentation of leimyoma?

Answer 38

Menorrhagia and infertility

Question 39

Occurrence of leiomyosarcoma?

Answer 39

Majority occur in women \>50 years of age

Question 40

Presentation of leiomyosarcoma?

Answer 40

Abnormal vaginal bleeding Palpable pelvic mass Pelvic pain

Question 41

Prognosis of leiomyosarcoma?

Answer 41

Poor, even it confined to uterus at the time of diagnosis NOTE - stage is the most important prognostic factor

Question 42

Staging of leiomyosarcoma?

Answer 42

Has the same staging system as endometrial stromal sarcoma (different from that of endometrial cancer)